Retrosplenial cortex enables context-dependent goal-directed sensorimotor transformation

The ability to dynamically adjust a behavioral response to a stimulus depending on context is of critical importance for animals. To investigate the neural basis supporting context-dependent sensory processing, we developed a behavioral task in which mice changed their response to a single whisker deflection according to a continuously present contextual cue. Through unbiased optogenetic inactivation mapping, we found that neuronal activity in sensory and motor cortices contributed to task execution and, interestingly, we uncovered an unexpected role of the retrosplenial cortex (RSC) for contextual integration. Widefield calcium imaging revealed that the RSC was the first dorsal cortical area to show context discrimination in response to whisker stimulation, followed by the whisker motor cortex. Finally, we combined optogenetic inactivation with calcium imaging to define causal context-dependent changes in sensorimotor processing. Our cortex-wide mapping experiments thus begin to define key cortical nodes for context-dependent sensorimotor transformation and highlight an important contribution of RSC.